The lithium ion is widely used in the therapy of affective disorders and substantial numbers of patients are chronically treated with this agent. Lithium has a variety of effects on renal function but these have generally been considered to be reversible when the drug is discontinued. Recently, however, lithium maintenance therapy has been incriminated as a cause of chronic interstitial nephritis and progressive renal insufficiency. Unfortunately, all the available studies are retrospective in design and only a few have utilized appropriate controls or provided detailed information on renal function prior to lithium administration. Consequently, these studies have yielded conflicting results. An intriguing by-product of some of these studies has been the suggestion that affective illness per se (and/or a variety of other psychotropic medications) may contribute to the development of renal disease in lithium-treated patients. Three years ago we initiated a prospective study of renal function in patients with affective disorders in which an extensive battery of baseline renal function studies, specifically designed to monitor for all known causes of chronic interstitial nephritis are performed prior to the initiation of lithium therapy and at selected intervals thereafter. Seventy-four patients have been entered to date and 42 patients remain active. Although is is still too early to reach conclusions, there is no definitive indication of a decrease in glomerular filtration rate to date. We propose to continue patient accrual for another 3 years and at the same time to recruit three separate control groups: patients with bipolar illness who have proved unresponsive to lithium maintenance therapy in the past and who are not currently receiving lithium, patients with recurrent or chronic depression who have never received lithium and are being treated with a variety of other psychotropic agents, and a group of normal volunteers. These control groups will be followed in an analogous fashion to the lithium group. The prospective design of this study, together with the use of 3 separate control groups will enable us to determine whether lithium maintenance therapy is associated with the development of renal disease. Moreover, it will provide important information on the potential association of affective disorders per se (and/or psychotropic medications other than lithium) with renal disease.